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Tuberculosis
Original article
The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis
  1. P J Dodd1,
  2. A J Prendergast2,3,
  3. C Beecroft1,
  4. B Kampmann4,5,
  5. J A Seddon4
  1. 1School of Health and Related Research, University of Sheffield, Sheffield, UK
  2. 2Blizard Institute, Queen Mary University of London, London, UK
  3. 3Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
  4. 4Centre of International Child Health, Department of Paediatrics, Imperial College London, London, UK
  5. 5Vaccines & Immunity Theme, MRC Unit The Gambia, The Gambia
  1. Correspondence to Dr PJ Dodd, School of Health and Related Research, Regent Court, 30 Regent Street, Sheffield S1 4DA, UK; p.j.dodd{at}sheffield.ac.uk

Abstract

Background Children (<15 years) are vulnerable to TB disease following infection, but no systematic review or meta-analysis has quantified the effects of HIV-related immunosuppression or antiretroviral therapy (ART) on their TB incidence.

Objectives Determine the impact of HIV infection and ART on risk of incident TB disease in children.

Methods We searched MEDLINE and Embase for studies measuring HIV prevalence in paediatric TB cases (‘TB cohorts’) and paediatric HIV cohorts reporting TB incidence (‘HIV cohorts’). Study quality was assessed using the Newcastle-Ottawa tool. TB cohorts with controls were meta-analysed to determine the incidence rate ratio (IRR) for TB given HIV. HIV cohort data were meta-analysed to estimate the trend in log-IRR versus CD4%, relative incidence by immunological stage and ART-associated protection from TB.

Results 42 TB cohorts and 22 HIV cohorts were included. In the eight TB cohorts with controls, the IRR for TB was 7.9 (95% CI 4.5 to 13.7). HIV-infected children exhibited a reduction in IRR of 0.94 (95% credible interval: 0.83–1.07) per percentage point increase in CD4%. TB incidence was 5.0 (95% CI 4.0 to 6.0) times higher in children with severe compared with non-significant immunosuppression. TB incidence was lower in HIV-infected children on ART (HR: 0.30; 95% CI 0.21 to 0.39). Following initiation of ART, TB incidence declined rapidly over 12 months towards a HR of 0.10 (95% CI 0.04 to 0.25).

Conclusions HIV is a potent risk factor for paediatric TB, and ART is strongly protective. In HIV-infected children, early diagnosis and ART initiation reduces TB risk.

Trial registration number CRD42014014276.

  • Tuberculosis

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/thoraxjnl-2016-209421

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    Footnotes

    • Twitter Follow Claire Beecroft @mscihta

    • Contributors Conceived and designed the study; undertook the review and data abstraction; drafted article: PJD, JAS. Designed the search strategy: CB, PJD, JAS. Statistical analysis: PJD. Commented on and revised article: all authors.

    • Funding Study funded by the STEP TB UNITAID grant to TB Alliance. The funders had no role in the design or execution of the study, nor the decision to publish. BK is funded by a programme grant from the MRC. AJP is funded by the Wellcome Trust (108065/Z/15/Z).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All data used in the analyses are available either in the main article or the online supplementary material.